CAJ | 학술논문

目的：探讨微小 RNA（miRNA）-122与抗结核药物性肝损伤的关系，为寻找抗结核药物性肝损伤的早期诊断标志物提供实验依据。方法昆明小鼠异烟肼（ INH）组每日1次 ig 给予2 mL INH （90 mg·kg-1），分别在连续给药1，3，5，7，14，21和28 d 后留取小鼠的血清和肝组织标本。采用全自动生化分析仪检测血清谷丙转氨酶（GPT）和谷草转氨酶（GOT）活性，生化法检测肝组织铜锌超氧化物歧化酶（Cu/ Zn-SOD）活性和丙二醛（mDA）含量，实时荧光定量 PCR 检测肝组织中 miRNA-122表达。结果药物处理后GPT 和 GOT 呈上升趋势，分别在14和21 d 后明显增加（P﹤0.05）；Cu/ Zn-SOD 和 mDA 分别在5 d 后呈下降趋势和上升趋势（P﹤0.05）。给药后 miRNA-122呈整体下降趋势，给药3 d 后 miRNA-122下降明显（P﹤0.05），并在14 d 下降到最小值0.58±0.02。相关性分析结果显示，miRNA-122和 GPT， Cu/ Zn-SOD，mDA 存在相关性，相关系数分别为-0.370，0.268和-0.298。结论 miRNA-122与 INH 所致抗结核药物性肝损伤的发生相关，且可作为 INH 所致抗结核药物性肝损伤的早期诊断标志物。
목적：탐토미소 RNA（miRNA）-122여항결핵약물성간손상적관계，위심조항결핵약물성간손상적조기진단표지물제공실험의거。방법곤명소서이연정（ INH）조매일1차 ig 급여2 mL INH （90 mg·kg-1），분별재련속급약1，3，5，7，14，21화28 d 후류취소서적혈청화간조직표본。채용전자동생화분석의검측혈청곡병전안매（GPT）화곡초전안매（GOT）활성，생화법검측간조직동자초양화물기화매（Cu/ Zn-SOD）활성화병이철（mDA）함량，실시형광정량 PCR 검측간조직중 miRNA-122표체。결과약물처리후GPT 화 GOT 정상승추세，분별재14화21 d 후명현증가（P﹤0.05）；Cu/ Zn-SOD 화 mDA 분별재5 d 후정하강추세화상승추세（P﹤0.05）。급약후 miRNA-122정정체하강추세，급약3 d 후 miRNA-122하강명현（P﹤0.05），병재14 d 하강도최소치0.58±0.02。상관성분석결과현시，miRNA-122화 GPT， Cu/ Zn-SOD，mDA 존재상관성，상관계수분별위-0.370，0.268화-0.298。결론 miRNA-122여 INH 소치항결핵약물성간손상적발생상관，차가작위 INH 소치항결핵약물성간손상적조기진단표지물。
OBJECTlVE To study the reIationship between microRNA(miRNA)-122 and Iiver injury in-duced by anti-tubercuIosis drugs,and to discover the new biomarkers for earIy diagnosis of this type of Iiver injury. METHODS mice were given 2 mL isoniazid oraIIy at 90 mg·kg-1 . BIood and Iiver tissue sampIes were coIIected at 1,3,5,7,14,21 and 28 d after administration of isoniazid. Serum gIutamic-pyruvic transaminase( GPT)and gIutamic-oxaIoacetic transaminase( GOT)IeveIs were determined using an automatic biochemicaI anaIyzer. Cu/ Zn-superoxide dismutase( Cu/ Zn-SOD ) activity and maIondiaIdehyde( mDA)content were detected by biochemicaI method. ReaI-time qPCR was used to measure the expression of miRNA-122. RESULTS GPT and GOT IeveIs were significantIy higher at 14 and 21 d(P﹤0.05)than in the controI. Cu/ Zn-SOD began to decIine whiIe mDA began to increase after 5 d(P﹤0.05). miRNA-122,which progressiveIy decreased after administration,was reduced to the mini-mum 0.58 ±0.02 at 14 d. There were good correIations between miRNA-122 and GPT,Cu/ Zn-SOD, mDA(the correIation coefficients were -0.370,0.268,and -0.298,respectiveIy),but no correIation with GOT was observed. CONCLUSlON The tissue miRNA-122 profiIe can be used as a sensitive marker for anti-tubercuIosis drug-induced Iiver injury,which couId contribute to the earIy diagnosis of Iiver injury.